tetano
Editor, Senior Moderator
Antioxid Redox Signal. 2019 Jun 13. doi: 10.1089/ars.2019.7727. [Epub ahead of print]
[h=1]MITOCHONDRIAL REACTIVE OXYGEN SPECIES CONTRIBUTE TO PATHOLOGICAL INFLAMMATION DURING INFLUENZA A VIRUS INFECTION IN MICE.[/h] To E[SUP]1[/SUP], Erlich J[SUP]2[/SUP], Liong F[SUP]3[/SUP], Luong R[SUP]4[/SUP], Liong S[SUP]5[/SUP], Esaq F[SUP]6[/SUP], Oseghale O[SUP]7[/SUP], Anthony D[SUP]8[/SUP], McQualter J[SUP]9[/SUP], Bozinovski S[SUP]10[/SUP], Vlahos R[SUP]11[/SUP], O'Leary JJ[SUP]12[/SUP], Brooks DA[SUP]13[/SUP], Selemidis S[SUP]14[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]AIMS:[/h] Reactive oxygen species (ROS) are highly reactive molecules generated in different subcellular sites or compartments; including endosomes via the NOX2-containing NADPH oxidase during an immune response and in mitochondria during cellular respiration. However, while endosomal NOX2 oxidase promotes innate inflammation to influenza A virus infection, the role of mitochondrial ROS (mtROS) has not been comprehensively investigated in the context of viral infection in vivo.
[h=4]RESULTS:[/h] Here, we show that pharmacological inhibition of mtROS, with intranasal delivery of mitoTEMPO, resulted in a reduction in airway/lung inflammation, neutrophil infiltration, viral titers, as well as overall morbidity and mortality in mice infected with influenza A virus (Hkx31, H3N2). MitoTEMPO treatment also attenuated apoptotic and necrotic neutrophils and macrophages in airway and lung tissue. At an early phase of influenza infection, i.e. Day 3 there were significantly lower amounts of IL-1b protein in the airways, but substantially higher amounts of Type I IFN-b following mitoTEMPO treatment. Importantly, blocking mtROS did not appear to alter the initiation of an adaptive immune response by lung dendritic cells, nor did it affect lung B and T cell populations that participate in humoral and cellular immunity. Innovation/Conclusion: Influenza virus infection promotes mtROS production, which drives innate immune inflammation and this exacerbates viral pathogenesis. This pathogenic cascade highlights the therapeutic potential of local mtROS antioxidant delivery to alleviate influenza virus pathology.
PMID: 31190565 DOI: 10.1089/ars.2019.7727
[h=1]MITOCHONDRIAL REACTIVE OXYGEN SPECIES CONTRIBUTE TO PATHOLOGICAL INFLAMMATION DURING INFLUENZA A VIRUS INFECTION IN MICE.[/h] To E[SUP]1[/SUP], Erlich J[SUP]2[/SUP], Liong F[SUP]3[/SUP], Luong R[SUP]4[/SUP], Liong S[SUP]5[/SUP], Esaq F[SUP]6[/SUP], Oseghale O[SUP]7[/SUP], Anthony D[SUP]8[/SUP], McQualter J[SUP]9[/SUP], Bozinovski S[SUP]10[/SUP], Vlahos R[SUP]11[/SUP], O'Leary JJ[SUP]12[/SUP], Brooks DA[SUP]13[/SUP], Selemidis S[SUP]14[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]AIMS:[/h] Reactive oxygen species (ROS) are highly reactive molecules generated in different subcellular sites or compartments; including endosomes via the NOX2-containing NADPH oxidase during an immune response and in mitochondria during cellular respiration. However, while endosomal NOX2 oxidase promotes innate inflammation to influenza A virus infection, the role of mitochondrial ROS (mtROS) has not been comprehensively investigated in the context of viral infection in vivo.
[h=4]RESULTS:[/h] Here, we show that pharmacological inhibition of mtROS, with intranasal delivery of mitoTEMPO, resulted in a reduction in airway/lung inflammation, neutrophil infiltration, viral titers, as well as overall morbidity and mortality in mice infected with influenza A virus (Hkx31, H3N2). MitoTEMPO treatment also attenuated apoptotic and necrotic neutrophils and macrophages in airway and lung tissue. At an early phase of influenza infection, i.e. Day 3 there were significantly lower amounts of IL-1b protein in the airways, but substantially higher amounts of Type I IFN-b following mitoTEMPO treatment. Importantly, blocking mtROS did not appear to alter the initiation of an adaptive immune response by lung dendritic cells, nor did it affect lung B and T cell populations that participate in humoral and cellular immunity. Innovation/Conclusion: Influenza virus infection promotes mtROS production, which drives innate immune inflammation and this exacerbates viral pathogenesis. This pathogenic cascade highlights the therapeutic potential of local mtROS antioxidant delivery to alleviate influenza virus pathology.
PMID: 31190565 DOI: 10.1089/ars.2019.7727